This invention relates to hexafluorohydroxyisopropyl heterocyclic antihypertensives.
Allied Chemical Corporation, in British Pat. No. 1,029,048 discloses hexahalohydroxyisopropyl aryl derivatives as intermediates in the preparation of aromatic carboxylic acids.
Jones, E. S., in U.S. Pat. Nos. 3,405,177 and 3,541,152 discloses hexahalohydroxyisopropyl aromatic amines useful as intermediates in the preparation of azo dyestuffs, polyesters, polyamides, insecticides, plasticizers, and pharmaceuticals.
Gilbert, E. E., in U.S. Pat. No. 3,532,753, discloses aromatic amino derivatives of hexahaloacetone useful as insecticides.
Many current antihypertensives produce unwanted side effects because of their undesirable mechanism of action. For example, guanethidine is an adrenergic neurone blocker, mecamylamine is a ganglion blocker, phenoxybenzamine is an .alpha.-adrenergic receptor blocker, and reserpine is a catecholamine depletor. Each of these mechanisms of action is undesirable because of the serious side effects produced.
The compounds of this invention appear to lower blood pressure by a desirable mechanism of action - direct peripheral vasodilation - and, therefore have a distinct advantage over the above undesirably acting antihypertensives.
Furthermore, these compounds do not appear to produce central nervous sytem effects such as those seen with clonidine and .alpha.-methyldopa administration. SUMMARY
According to this invention there is provided compounds of Formula I, processes for their manufacture, pharmaceutical compositions containing them, and methods of using them to treat hypertension in mammals. ##STR1## where R.sub.1 and R.sub.2 taken together = ##STR2## (b) --(CH.sub.2).sub.4-- (c) --(CH.sub.2).sub.5--
where PA1 R = methyl or ethyl; PA1 R.sub.3 = H, methyl, or ethyl; and PA1 R.sub.4 = C.sub.1 -C.sub.5 carbons which can be straight-chained, branched-chained, or alicyclic. PA1 R and R' independently = H, methyl, or ethyl PA1 when n = 1; PA1 R and R' = hydrogen when n = 2 or 3; and PA1 R.sub.3 = h, methyl, and ethyl; and PA1 R.sub.4 = c.sub.1 --c.sub.5 carbons which can be straight-chained, branched-chained, or alicyclic.